The active
morphine metabolite,
morphine-6-glucuronide (M-6-G), may contribute to both the
analgesia and the adverse effects observed during
morphine (MOR)
therapy. To evaluate the relationship between M-6-G and adverse effects, we measured steady-state plasma concentrations of MOR and M-6-G and concurrently noted the presence or absence of moderate to severe
cognitive impairment or
myoclonus in 109
cancer patients who were receiving either oral (n = 71) or parenteral (n = 38)
morphine. MOR and M-6-G plasma concentrations were determined by HPLC with electrochemical detection. The presence of
cognitive impairment or
myoclonus was analyzed in relation to molar M-6-G/MOR ratio, age,
morphine dose, the use of other centrally acting drugs, renal function (blood
urea nitrogen (BUN) and serum
creatinine), hepatic function (serum
bilirubin, serum glutamic oxalacetic
transaminase (
SGOT), and alkaline phosphotase) and serum
lactate dehydrogenase (LDH). The patient population consisted of 60 women and 49 men. The mean age was 51.5 years (range: 10-85 years). The mean
morphine dose (total dose-prior 48 h) was 486 mg (range: 40-4800 mg) for the oral group and 931 mg (range: (10-9062 mg) for the parenteral group. The mean molar M-6-G/MOR ratios were 6.1 (SD: 18.2; range: 0.01-153.3) for the oral treatment group and 2.7 (SD: 4.16; range: 0.05-23.8) for the parenteral treatment group. Overall, the M-6-G/MOR ratio demonstrated a moderate but significant correlation with BUN (r = 0.4; P < 0.001) and
creatinine (r = 0.45; P < 0.001) levels, but not with the other clinical variables examined.(ABSTRACT TRUNCATED AT 250 WORDS)